An integrin avb3-c-Src oncogenic unit promotes anchorage-independence and tumor progression (Nat Med, 2009, 15:1163-1169)

報告日期: 2010/03/19
報告時間: 15:10/16:00
報告學生: 陳柏谷(英文報告)
講評老師: 呂增宏
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990319-1.pdf

An integrin αvβ3–c-Src oncogenic unit promotes anchorage-independence and tumor progression

Jay S Desgrosellier1, Leo A Barnes1, David J Shields1, Miller Huang1, Steven K Lau1, Nicolas Prévost2, David Tarin1,Sanford J Shattil2 & David A Cheresh1

 

Nature Medicine. 2009 Oct;15(10):1163-9.

 

Speaker陳柏谷

Commentator呂增宏 老師

Date2010/03/19

Time : 15:10-16:00

PlaceRoom 602

 

 

Abstract

Integrins regulate a wide range of adhesion-dependent effects in tumor cells including proliferation, survival, migration and invasion through activation of focal adhesion kinase (FAK) and Src family kinase (SFK). Integrin αvβ3 is expressed on the most progressive tumor cells and is correlated with increased lymph node metastasis. Integrin αvβ3 mediated anchage-independent role was rare described. Firstly, authors showed that the expression of Integrin αvβ3 on tumor cells enhanced anchorage-independent growth in soft agar assay and increased lymph node metastasis in vivo. Secondary, authors demonstrated that integrinβ3 directly interacted with c-Src by Co-IP analysis, and the interaction leads to activation of c-Src and phosphorylation of Crk-associated substrate (CAS) in a FAK independent manner. Finally, the authors showed that either inhibition of c-Src kinase activity by dasatinib or silencing of the expression of c-Src or Integrin αvβ3 resulted in suppression of anchorage-dependent growth and metastasis in vivo. In conclusion, Integrin αvβ3 mediated anchorage-independent growth of cnacer through recruitment and activation of c-Src.

 

Reference

1.    Guo, W. & Giancotti, F.G. Integrin signalling during tumour progression. Nat. Rev. Mol. Cell Biol. 5, 816–826 (2004).

2.    Ginsberg, M.H., Partridge, A. & Shattil, S.J. Integrin regulation. Curr. Opin. Cell Biol. 17, 509–516 (2005).

3.    Summy, J.M. & Gallick, G.E. Src family kinases in tumor progression and metastasis. Cancer Metastasis Rev. 22, 337–358 (2003).